The RNA world that came before life might have gotten a big boost from iron.

Life may have started from an RNA world, where RNA both carried genetic information and catalyzed chemical reactions, jobs that are now divided between DNA and proteins. But sussing out the chemistry of the RNA world is challenging, not least because we’ll never really know what metals and molecules were present on the early Earth. Scientists have some clues from the chemistry of rocks, computer models, and lab experiments.

New research suggests that RNA on the early Earth could have interacted with different metals than it does today. Magnesium currently helps our RNA fold into the proper shapes for catalysis. Changing that metal to iron could increase the types of reactions that could be catalyzed by early RNAs.

Iron dissolved in watery pools was plentiful on the oxygen-free early Earth. Once photosynthetic organisms appeared and started pumping out oxygen, that iron turned to rust, and was trapped in rocks as bands still visible today. Since the RNA world is thought to have existed before this Great Oxidation Event, Loren Williams at Georgia Institute of Technology and his colleagues wondered if RNA on early Earth could have bound iron.

First, the researchers modeled of a snippet of the RNA backbone – just one sugar flanked by two phosphate groups. They plunked a magnesium or an iron ion in between the phosphates and calculated the most stable shape of the backbone. Both backbones had the same shape, regardless of metal ion inside.

Knowing that an iron ion (Fe2+) could fit in the same place as Mg2+ in RNA, the researchers tested modern RNA enzymes, or ribozymes, to see if they would still function with iron under oxygen-free conditions. One ribozyme, a ligase that connects RNA molecules, was actually 25 times more active using iron than magnesium. The other ribozyme snipped RNA apart three times faster when it bound iron instead magnesium.

Not only can modern RNA enzymes bind iron, they also work more efficiently using that ion. What else might iron do for the function of early ribozymes? Iron can transfer electrons more efficiently than magnesium. Ancient ribozymes holding iron could likely perform a broader range of reactions than modern ones, since they could shuffle electrons between molecules more efficiently. (Most of basic metabolism, like conversion of sugars into usable energy, involves electron transfer reactions.)

An RNA world with iron would be the RNA world on steroids, the researchers write. Over time, less-reactive magnesium ions may have replaced the iron ions because they better stabilize folded RNAs.

The researchers plan to continue to study the chemistry of iron-RNA complexes, looking for reactions not possible with magnesium.

Making molecules that resemble ones we find in life today is simple. Stanley Miller did it in 1953, when he combined ammonia, hydrogen, methane and water vapor in a jar and zapped the mixture with a lightning bolt. In that primordial soup, Miller found building blocks of proteins and simpler molecules like urea that could be used to build more complicated biochemicals. Analyzing that mixture more than 50 years later with modern methods, researchers found even more amino acids than Miller originally thought.

Now, many researchers are looking into how collections of these simple molecules started interacting. “The big challenge today is figuring how you select, concentrate, and assemble all of those molecules into a larger lifelike system, one which starts to make copies of itself,” geophysicist Robert Hazen of the Carnegie Institution of Washington told the Economist this week. “And that remains a huge mystery.”

Catalysts, whether salts, metals or nucleic acids, can help with the selection process. They guide chemical reactions away from a sticky mix of products to a group of specific molecules. So identifying early catalysts could help scientists identify possible chemical reactions that could lead to the building blocks of life.

Melissae Fellet
Melissae is obsessed with electrons, atoms and molecules. She writes about chemistry, physics and technology and holds a PhD in chemistry from Washington University in St. Louis. Twitter@mfellet

19 Reader Comments

Making molecules that resemble ones we find in life today is simple. Henry Miller did it in 1953, when he combined ammonia, hydrogen, methane and water vapor in a jar and zapped the mixture with a lightning bolt.

Making molecules that resemble ones we find in life today is simple. Henry Miller did it in 1953, when he combined ammonia, hydrogen, methane and water vapor in a jar and zapped the mixture with a lightning bolt.

You mean Stanley Miller.

I cannot believe i missed that. Thanks for catching it. (Maybe if i didn't already know the name Henry Miller, it would have stood out?)

Making molecules that resemble ones we find in life today is simple. Henry Miller did it in 1953, when he combined ammonia, hydrogen, methane and water vapor in a jar and zapped the mixture with a lightning bolt.

You mean Stanley Miller.

I cannot believe i missed that. Thanks for catching it. (Maybe if i didn't already know the name Henry Miller, it would have stood out?)

May not be all that wrong. After all, Henry Miller wrote "The Crucible" and the "molecules" get together the same way today as they did then.

So similar to how we apparently have to slow down as we run out of cheap fuel, RNA slowed down as it ran out of easy to access iron ions and had to look for alternatives?

Btw, what will happen if modern day cells are given a high dosage of these iron ions?

From what I understood in the article, the RNA that bound iron were also a lot more unstable than RNA that binds magnesium. I'm guessing that iron would probably not be such a good idea for modern-day stable RNA.

So similar to how we apparently have to slow down as we run out of cheap fuel, RNA slowed down as it ran out of easy to access iron ions and had to look for alternatives?

Btw, what will happen if modern day cells are given a high dosage of these iron ions?

From what I understood in the article, the RNA that bound iron were also a lot more unstable than RNA that binds magnesium. I'm guessing that iron would probably not be such a good idea for modern-day stable RNA.

My laymen's guess is that oxygen in the modern atmosphere would be bad for RNA using iron. The old atmosphere had little to no oxygen.

So similar to how we apparently have to slow down as we run out of cheap fuel, RNA slowed down as it ran out of easy to access iron ions and had to look for alternatives?

Btw, what will happen if modern day cells are given a high dosage of these iron ions?

Non-protein bound, uncoordinated ('free') iron ions are toxic to cells under aerobic conditions as they catalyse the production of reactive oxygen species such as superoxide, hydrogen peroxide and the hydroxyl radical.

The oxygenation of the atmosphere was likely the largest ever extinction event.

This is one of two recent papers that can be taken to build a theory implying that. That an RNA world preceeded the current DNA cellular world is pretty well established today. We have many fossils in the cells (RNA transcription of genes, RNA catalytic center in ribosomes, early RNA tagging of proteins going to the cellular membrane). And it predicts how the interlocking between todays proteins producing DNA and DNA producing proteins was preceded by RNA catalysts and RNA genomes.

We can predict that early RNA organisms lived in a world of little oxygen and hence much iron, before the oxygenation of the atmosphere. The paper tests that nicely, since it finds that iron ions works better than today's magnesium ions for RNA catalysts:

I believe the authors suggest somewhere that the increase in reactivity also tests a prediction that RNA was selected over other similar compounds, as it is particularly adept in taking advantage of the plentiful iron. And of course the high reactivity with iron means RNA is a much more realistic alternative as early catalyst.

The interesting point here though is that Benner, well known expert on origins of life, sees this as an implication that the change from RNA to protein catalysis can be tied to the time of oxygenation (see the link). More specifically, it would be the point where an eventual mixture of catalysts would latest see the RNA mostly replaced. It is an excellent bottleneck constraint explaining why RNA world life disappeared in toto.*

This coincides with the recent phylogeny of Braakman and Smith on evolution of metabolism, which according to them shows sign of divergence precisely after the creation of the oxygen atmosphere. The pre-LUCA would have been fitted with a curiously robust, redundant and over evolutionary time stable metabolic network that were fixed by “imprecise or unreliable enzyme function … or unreliable regulation”.

They point out that this would leave open the possibility of chemical evolution at early stages, but it could also be a signal of a disappearing RNA world. ["The Emergence and Early Evolution of Biological Carbon-Fixation", Braakman and Smith, PLoS Comp Biol, 2012.]

The second paper raises the question: if not a later cyanobacteria were responsible for the atmospheric change, what was? A blog article at the time pointed to a paper where a presumed global glaciation at the time lead to the first UV-driven release of massive amounts of oxygen.

The initial pulses of the poisonous substance would have tipped the balance and eventually lead up to a diversity of oxygenating photosynthesizers. In effect reversing the usual oxygenating photosynthesis – oxygen – glaciation supposed order of events.

Needless to say, the RNA to DNA world bottleneck could, most likely would, have wiped out nearly all existing life.——————* Except possibly surviving as some parasitically simplified RNA viruses akin to what some people believed happened to the putative DNA Megavirus ancestor.

One way early evolution would have been on top of the Archean world's rapid changes in environment could have been shorter generation cycles.

Another proposed mechanism is suggested by the RNA world, since RNA genomes would have consisted of shorter stretches genetic material than the stabler DNA. In fact it is believed RNA cells would have had swarms of RNAs that comprised genes or parts of genes many times copied, with less faithful replication akin to swarms of rapidly mutating HIV viruses in people today, so called quasi-species. The HIV virus that finally cause aids is not much like the virus that once infected that person.

Mind that there is no fast and hard relationship between metabolism and life span. Animals have a self-limiting mechanism for cellular replication, but it is believed to avoid cancer that ultimately derive from oncogenes. Plants and fungus have virtually no cancer problems, as they have no critical organs and can simply grow healthy tissue around similar pathological growths. And they can become much older while happily growing faster than animals.

Bacteria and perhaps archaea has another life length limit. They accumulate biochemical and structural damage in one preferential cell "parent", which inevitably die after ~ 200 cell divisions. But I would guess such damage would mostly constitute hard to disassemble proteins that they can't dispel either.

RNA cells may not have labored under such a problem - no or little proteins. So who knows, maybe they were individually eternal, modulo cell divisions, and had to rely on less faithful copying to evolve and survive instead of gene culling by darwinian selection.

Normal stars can fuse lighter elements into heavier and heavier elements up as far as iron.That is where the fusion stops for normal starsOur own sun will never create any element heavier than iron.But much more massive stars can fuse iron into heavier elements.What do you see when they do fuse iron?You see a Supernova; when the massive star explodes and it outshines the galaxy it is in.

What's especially interesting in the discussion is an implied logic train. The events that caused iron fusion, iron-based RNA and DNA's eventual ascension at least on this planet are due to a certain amount of cosmic randomness in combination with a statistical certainty. It would be interesting to see what replaces DNA-based life. Sometime, somewhere a star had to explode attempting to fuse iron to enable RNA based life to begin. When a kink in the distribution of iron ions on the planet occurs, a mutated bacteria generates oxygen as a waste product that eventually wipes out the iron based RNA opening the way for DNA based life. Each step lifeforms are getting much more complicated, yet more ordered and longer-lived. Are we really just intelligent star dust? At what point does physical matter factor out of the equations?